Is P2RY2 p.Pro189Ser (c.565C>T) pathogenic?

P2RY2 p.Pro189Ser (c.565C>T) is classified Uncertain significance in P2RY2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.2383); Very rare (popmax 0.00267%, afr).

How common is P2RY2 p.Pro189Ser (c.565C>T) in the general population?

P2RY2 p.Pro189Ser (c.565C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about P2RY2 p.Pro189Ser (c.565C>T)?

AlphaMissense predicts likely benign (score 0.2383) — an in-silico prediction, not a clinical call.

P2RY2 p.Pro189Ser

c.565C>T · rs1371982260 · VCV2240249

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2383 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2383	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -11.11	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP -0.003, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 1,130 bp · p 0.024 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,932 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000249% 4/1,609,090 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,466
Remaining individualsnot grpmax-eligible	0.0016%	62,418
European (non-Finnish)	8.48e-05%	1,179,585

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: P2RY2
Protein: p.Pro189Ser
Coding: c.565C>T
MANE Select: NM_002564
dbSNP: rs1371982260
Type: single nucleotide variant
Location: chr11:73234724 (GRCh38)
Gene constraint: LOEUF 1.917 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 79.11 · 3 PDB
Residue 189: a β-strand

Full P2RY2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

P2RY2 p.Pro189Arg Uncertain significance ★ ⚠ same residue
P2RY2 p.Ala176Thr Uncertain significance ★ ⚠ same type
P2RY2 p.Ala252Thr Uncertain significance ★ ⚠ same type
P2RY2 p.Ala287Val Uncertain significance ★ ⚠ same type
P2RY2 p.Ala309Pro Uncertain significance ★ ⚠ same type
P2RY2 p.Ala80Thr Uncertain significance ★ ⚠ same type
P2RY2 p.Ala94Asp Uncertain significance ★ ⚠ same type
P2RY2 p.Ala94Val Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/p2ry2-p-pro189ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown